We propose to examine the changes in cholinergic function which accompany aging, and to measure the effect of neuroleptic drugs upon these changes. We hypothesize specifically that neuroleptics alter the activity of choline acetyltransferase (CAT), the enzyme which catalyzes the synthesis of acetylcholine, and that these drugs may affect the enzyme differently in aged and in non-aged populations. We propose to measure the kinetics and regulation of CAT in both mature adult and aged population of mice. We shall examine several potential sources of regulation of the enzyme. In preliminary work, we have succeeded in purifying CAT from rat brain by about 50,000 fold, to homogeneity of about 50%. We shall use this preparation as the basis of techniques with which to obtain monospecific antibodies, either by continuing the purification to obtain completely homogeneous enzyme by generating monoclonal antibodies by means of hybridomas. Once obtained, the antibodies will also be used to study CAT in aged mice, and to compare the properties of the enzyme in aged and mature adult mice.